Severe acute respiratory syndrome (SARS) is a potentially fatal disease that appears to have originated in the Guandong Province of China in the fall of 2002. The disease is caused by a new human coronavirus (CoV), named the SARS-CoV, which is unlike any previous known coronavirus, but classified among the group II coronaviruses like MHV. The goals of this proposal include the systematic deletion of each accessory ORF singly and then in combinations of the accessory ORFs of the SARS-CoV. I will use these deletion mutants to test the hypothesis that one or more accessory ORFs are responsible for modulating the host innate immune response. I will analyze the anti-viral response in Caco2, MA104 and Human Airway Epithelial (HAE) cells to establish at what level in the anti-viral pathway the interferon-antagonist proteins of SARS are acting, as well as how mutants in these SARS genes effect pathogenesis. [unreadable] [unreadable]